The 8th year of this program project has seen the completion of 20 epidemiologic studies, for a total of nearly 100, with 40 others still in progress. This remarkable output reflects the productivity of a unique data file built on the extensive Mayo Clinic records linkage system, complemented by the records of other medical resources in and around Olmsted County, Minnesota. Ready access to well-defined sets of medical histories is provided by diagnostic categories for this population over a period of 35 years or more. This year we moved toward the use of this resource on an urgent basis to attack questions on etiology through case-control comparisons by identifying new risk factors and through prospective studies to evaluate specific etiologic agents, e.g., a completed study of the incidence of hypospadias revealed a polygenic pattern which warrants further study; evidence was obtained that maternal usage of certain anticonvulsants in the first trimester is related to cleft palate and congenital heart disease in offspring; and a prospective study has provided needed estimates on the risk of malformations and genitourinary cancer in offspring exposed prenatally to estrogens. Studies underway and nearing completion include incidence, risk factors and outcome of ischemic heart disease, the relationship of benign breast lesions to subsequent breast carcinoma, a comprehensive study of diabetes and its complications, the interrelation of heart disease and stroke, a comparison of the incidence of breast cancer in a rural and urban population, an extensive study of epilepsy covering a 32-year period, etc. Our data bank continues to be utilized by residents, and advanced degree candidates of the Mayo Clinic and other universities and by epidemiologists from various Federal health agencies. The program has provided an environment for medical students and graduate students to enhance their training in epidemiology and statistics; it has grown each year in scope and in depth and serves as an excellent example of the appropriate application of the program project mechanism to clinical and epidemiologic research.